Assessment of Cerebral Autoregulation and Cerebral Perfusion in Patients with Sickle Cell Disease using Frequency-Domain Near-Infrared Spectroscopy.

Cerebral small vessel disease is a neurological complication of sickle cell disease (SCD) associated with cerebral hypoperfusion and cognitive dysfunction. Early and prompt detection is important for prevention and treatment, preferably with a non-invasive, inexpensive point-of-care test. Impaired cerebral autoregulation (CA) is a marker of cerebral small vessel disease, so we evaluated whether imaging hemodynamic changes in the microvasculature can assess abnormal CA in patients with SCD. We instructed patients (n=13) and healthy controls (n=14) to breathe at three different rates using a metronome while frequency-domain near-infrared spectroscopy (FDNIRS), a non-invasive optical imaging method, measured the phase delay and amplitude ratios between oxygenated and deoxygenated hemoglobin concentration changes. These measurements served as a surrogate measure of CA efficiency. We applied a mathematical hemodynamic model to calculate blood transit times and CA efficiency. We found that patients with SCD had significantly lower phase difference between oxyhemoglobin and deoxyhemoglobin oscillations (-320° to -340°) than controls (-200° to -240°), indicating differences in CA and blood transit time between the groups. Cerebral tissue oxygen saturation was reduced in patients with SCD (63.1% ± 7.8%) compared to controls (66.1% ± 4.7%). The hemodynamic model further found a significant difference in the capillary transit time and autoregulation cutoff frequency between SCD (1.88 ± 0.14s; 0.016 ± 0.0033Hz) and controls (0.71 ± 0.24s, p<0.05; 0.02 ± 0.0052Hz, p<0.05). Herein, we present preliminary evidence of the utility of NIRS to monitor CA in SCD; NIRS may represent a new screening method for cerebral small vessel disease in SCD.